Sensory neuropathy and signs of central sensitization in patients with peripheral arterial disease

Abstract

Patients with peripheral arterial disease (PAD) may develop a broad range of peripheral nerve dysfunctions including pain and sensory deficiencies due to chronic ischemia mostly involving the lower limbs. To investigate the degree of sensory abnormalities in such patients quantitative sensory testing (QST) might be a useful tool. Forty-five patients and 20 controls were enrolled in the present study and underwent QST according to the protocol of the German Research Network on Neuropathic Pain. PAD was graded according to the Rutherford classification. PAD patients were divided into two groups: 16 patients with critical limb ischemia (severe PAD) and 29 patients with intermittent claudication (moderate PAD). QST revealed impaired cold and warm detection, increased mechanical and vibration detection thresholds, and increased perceptual wind-up on the affected leg (all p < 0.001). Paradoxical heat sensation ( p < 0.05) and dynamic mechanical allodynia ( p < 0.01) were also observed. Subgroup analysis of patients without diabetes (control n = 20, moderate PAD n = 21, severe PAD n = 8) confirmed most of these findings. In patients with severe PAD, sensory deficits were more pronounced than in patients with moderate PAD and were detected even in the face. These data indicate that QST can detect sensory abnormalities in PAD patients. While the pattern of decreased perception suggests deafferentation for Aβ-, Aδ-, and C-fiber inputs, the presence of allodynia suggests that central sensitization also plays a role in the pain state of PAD patients. Subgroup analysis points towards a PAD-associated peripheral neuropathy independent of diabetes.